Korean Diabetes J.  2008 Oct;32(5):445-452. 10.4093/kdj.2008.32.5.445.

The Effect of Rosiglitazone and Metformin Therapy, as an Initial Therapy, in Patients with Type 2 Diabetes Mellitus

• Sohn TS
• Lee JI
• Kim IJ
• Min KW
• Son HS

• KMID: 2298083
• DOI: http://doi.org/10.4093/kdj.2008.32.5.445

Abstract

BACKGROUND
Type 2 diabetes is usually preceded by a long and clinically silent period of increasing insulin resistance. The purpose of this study is to demonstrate that rosiglitazone and metformin fixed-dose combination therapy (RSG/MET) will safely and effectively control glycemia as a first line of oral therapy, better than rosiglitazone (RSG) or metformin (MET) monotherapy in Korean type 2 diabetes patients.
METHODS
This study was a 32-week, multicenter, randomized, double-blind study. Twenty-seven type 2 diabetes patients (males 14; females 13) were included and randomly divided into the rosiglitazone, metformin group, or rosiglitazone /metformin combination groups. The primary objective of this study was to determine the change in HbA1c from baseline (week 0) to week 32. The secondary end-points were to determine changes in fasting plasma glucose (FPG) and homeostasis model assessment insulin resistance (HOMA-IR), from baseline to week 32. Other cardiovascular risk markers were also assessed.
RESULTS
At week 32, there were significant reductions in HbA1c and FPG, in all three treatment groups. There was no statistical difference in HbA1c among the three groups, but the decrease in FPG in the RSG/MET group was statistically significant compared to the MET group (P < 0.05). RSG/MET significantly reduced HOMA-IR at week 32 compared to baseline, but there was no difference among the three groups. RSG/MET significantly decreased high-sensitive C-reactive protein (hs-CRP) value at week 32, compared to baseline. There were increases in adiponectin from baseline to week 32 in the RSG and RSG/MET groups, and the increase in the RSG/MET group was statistically significant compared to that of the MET group (P < 0.05). At week 32, there was a significant decrease in plasminogen activator inhibitor-1 (PAI-1) in all three treatment groups, but no statistically significant difference among them. The RSG/MET group significantly decreased in terms of urinary albumin-creatinine ratio at week 32, compared to baseline.
CONCLUSIONS
In this study, rosiglitazone and metformin combination therapy was effective in glycemic control as an initial therapy, and it improved cardiovascular risk markers in Korean type 2 diabetes patients.

Keyword

Metformin; Rosiglitazone; Type 2 diabetes

MeSH Terms

Adiponectin
C-Reactive Protein
Diabetes Mellitus, Type 2
Double-Blind Method
Fasting
Female
Glucose
Homeostasis
Humans
Insulin Resistance
Metformin
Plasma
Plasminogen Activators
Thiazolidinediones
Adiponectin
C-Reactive Protein
Glucose
Metformin
Plasminogen Activators
Thiazolidinediones

Reference

1. The DCCT Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993. 329:977–986.

2. UK Prospective Diabetes Study (UKPDS) Group. UKPDS) Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998. 352:837–853.

3. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999. 281:2005–2012.

4. Wright A, Burden AC, Paisey RB, Cull CA, Holman RR. Sulfonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the U.K. Prospective Diabetes Study (UKPDS 57). Diabetes Care. 2002. 25:330–336.

5. DeFronzo RA. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes. Diabetes Rev. 1997. 5:177–269.

6. Kein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care. 1995. 18:258–268.

7. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes. JAMA. 2002. 287:360–372.

8. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985. 28:412–419.

9. Welsh M, Mares J, Oberg C, Karlsson T. Genetic factors of importance for beta-cell proliferation. Diabetes Metab Rev. 1993. 9:25–36.

10. Kahn SE. The relative contribution of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003. 46:3–19.

11. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000. 321:405–412.

12. Park JY, Lee KU, Kim CH, Kim HK, Hong SK, Park KS, Lee HK, Min HK. Past and current obesity in Koreans with non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1997. 35:49–56.

13. Yoon KH, Ko SH, Cho JH, Lee JM, Ahn YB, Song KH, Yoo SJ, Kang MI, Cha BY, Lee KW, Son HY, Kang SK, Kim HS, Lee IK, Bonner-Weir S. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab. 2003. 88:2300–2308.

14. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, Kravitz BG, Lachin JM, O'Neill MC, Zinman B, Viberti G. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006. 355:2427–2443.

15. Wiernsperger NF, Bailey CJ. The antihyperglycaemic effect of metformin: therapeutic and cellular mechanisms. Drugs. 1999. 58:31–39.

16. Miyazaki Y, Glass L, Triplitt C, Matsuda M, Cusi K, Mahankali A, Mahankali S, Mandarino LJ, DeFronzo RA. Effect of rosiglitazone on glucose and non-esterified fatty acid metabolism in Type II diabetic patients. Diabetologia. 2001. 44:2210–2219.

17. Freed MI, Ratner R, Marcovina SM, Kreider MM, Biswas N, Cohen BR, Brunzell JD. Effects of rosiglitazone alone and in combination with atorvastatin on the metabolic abnormalities in type 2 diabetes mellitus. Am J Cardiol. 2002. 90:947–952.

18. Bennett PH, Lee ET, Lu M, Keen H, Fuller JH. Increased urinary albumin excretion and its associations in the WHO Multinational Study of Vascular Disease in Diabetes. Diabetologia. 2001. 44:S37–S45.

19. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med. 1997. 157:1413–1418.

20. Bakris G, Viberti G, Weston WM, Heise M, Porter LE, Freed MI. Rosiglitazone reduces urinary albumin excretion in type II diabetes. J Hum Hypertens. 2003. 17:7–12.

21. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993. 16:434–444.

22. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998. 339:229–234.

23. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med. 2002. 347:1557–1565.

24. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007. 356:2457–2471.

25. Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP, Komajda M, McMurray JJ. Rosiglitazone evaluated for cardiovascular outcomes-an interim analysis. N Engl J Med. 2007. 357:28–38.